Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Anticancer Phytochemical Delivery: Advances, Challenges, and Future Prospects.

Phytochemicals exhibit a broad spectrum of pharmacological activities, including significant anticancer potential. However, their clinical translation is often hampered by poor aqueous solubility, low bioavailability, and chemical instability. Lipid-based nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have proven to be effective strategies for addressing these challenges. These nanocarriers improve the solubility, stability, and bioavailability of phytochemical-based anticancer agents, while enabling controlled and tumor-specific drug release. Encapsulation of anticancer phytochemicals such as curcumin, quercetin, resveratrol, silymarin, and naringenin in SLNs and NLCs has demonstrated improved therapeutic efficacy, cellular uptake, and reduced systemic toxicity. Co-delivery strategies, combining multiple phytochemicals or phytochemical-synthetic drug pairs, further contribute to synergistic anticancer effects, dose reduction, and minimized side effects, particularly important in complex cancers such as glioblastoma, breast, and colon cancers. This review presents a comparative overview of SLNs and NLCs in terms of formulation methods, in vitro characterization, and classification of key phytochemicals based on chemical structure and botanical sources. The roles of these lipidic carriers in enhancing anticancer activity, challenges in formulation, and recent patent filings are discussed to highlight ongoing innovations. Additionally, hybrid lipid-polymer nanoparticles are introduced as next-generation carriers combining the benefits of both systems. Future research should aim to develop scalable, biomimetic, and stimuli-responsive nanostructures through advanced surface engineering. Collaborative interdisciplinary efforts and regulatory harmonization are essential to translate these lipid-based carriers into clinically viable platforms for anticancer phytochemical delivery.